EP0572910B1 - Membrane pour dialyse à base d'éthers de polysaccharides - Google Patents

Membrane pour dialyse à base d'éthers de polysaccharides Download PDF

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Publication number
EP0572910B1
EP0572910B1 EP93108473A EP93108473A EP0572910B1 EP 0572910 B1 EP0572910 B1 EP 0572910B1 EP 93108473 A EP93108473 A EP 93108473A EP 93108473 A EP93108473 A EP 93108473A EP 0572910 B1 EP0572910 B1 EP 0572910B1
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Prior art keywords
dialysis membrane
membrane according
ether
spinning solution
polysaccharide
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EP93108473A
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German (de)
English (en)
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EP0572910A1 (fr
Inventor
Michael Dr. Diamantoglou
Gustav Dünweg
Thomas Dr. Rintelen
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Akzo Nobel NV
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Akzo Nobel NV
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06—Organic material
    • B01D71/08—Polysaccharides
    • B01D71/12—Cellulose derivatives
    • B01D71/22—Cellulose ethers
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B11/00—Preparation of cellulose ethers
    • C08B11/16—Aryl or aralkyl ethers

Definitions

  • the invention relates to a dialysis membrane for hemodialysis in the form of flat films, tubular films or hollow threads made of polysaccharide ether.
  • Dialysis membranes for hemodialysis place very high demands on biocompatibility, so that the blood flowing past the membranes is affected as little as possible.
  • the main parameters of biocompatibility are thrombogenicity, leucopenia and complement activation.
  • EP-A-0 459 293 discloses a dialysis membrane for hemodialysis in the form of flat foils, tubular foils or hollow fibers made of polysaccharide ethers, which is characterized in that the polysaccharide ether has a formula reproduced structure, in which Cell is the skeleton of the unmodified cellulose molecule or of the chitin molecule in each case without hydroxyl groups, s is 3 for the unmodified cellulose molecule and 2 for the chitin molecule and x corresponds to the degree of etherification, which is in the range from 0.08 to (s - 0.4) and where R is an optionally substituted alkyl, alkenyl and / or alkynyl and / or cycloalkyl and / or cycloalkenyl and / or cycloalkynyl and / or arylalkyl and / or arylalkenyl and / or arylalkynyl and / or
  • the polysaccharide is relatively highly substituted and also contains ionic groups, which also increase thrombogenicity.
  • EP-A-0 550 879 which falls under Article 54 (3) EPC, proposes to improve the biocompatibility of cellulosic flat membranes by coating them with cellulose ethers and / or cellulose esters and / or cellulose carbamates during or after their production , the degree of modification of these modified celluloses serving as coating agents being in the range from 0.002 to 3.
  • EP-A-0 339 502 a process for the subsequent chemical modification of cellulosic dialysis membranes for the purpose of improving the biocompatibility is known, in which dissolved modification reagents are passed past a surface of the dialysis membrane. Such a procedure is associated with very complex measures and also requires very intensive washing processes.
  • dialysis membranes made of synthetic or natural polymers when used in artificial kidneys, can very easily cause blood to clot, which is largely prevented by appropriate medicinal treatment, the dialysis treatment of a kidney patient with dialyzers occurs in the membranes made from regenerated cellulose contain a temporary drop in leukocytes in the first period of dialysis treatment. This effect is known as leukopenia.
  • Leukopenia is a decrease in the number of leukocytes (white blood cells) in the bloodstream.
  • the number of white blood cells in humans is approximately 4000 to 12000 cells / mm3.
  • Dialysis leukopenia is most pronounced 15 to 20 minutes after the start of treatment, and the neutrophils (those that can be stained with neutral or simultaneously stained with acid and basic dyes) can almost completely disappear. After that, the number of leukocytes recovers to almost the original value or exceeds it within about an hour. If a new dialyzer is connected after the leukocytes have recovered, leukopenia occurs again to the same extent.
  • the complement system within the blood serum is a complex, multi-component plasma enzyme system that serves in various ways to ward off damage caused by the invasion of foreign cells (bacteria, etc.). If antibodies against the penetrating organism are present, the complex can be activated in a complement-specific manner by the complex of the antibodies with antigenic structures of the foreign cells, otherwise the complement activation takes place in an alternative way through special surface features of the foreign cells.
  • the complement system is based on a large number of plasma proteins. After activation, these proteins react with each other specifically in a certain order and in the end a cell-damaging complex is formed that destroys the foreign cell.
  • Peptides are released from individual components, which trigger inflammation symptoms and can occasionally also have undesirable pathological consequences for the organism. It is believed that activation in regenerated cellulose hemodialysis membranes occurs via the alternative route. These complement activations are objectively determined by determining the complement fragments C3a and C5a.
  • complement activation was assessed on the basis of fragments C5a.
  • 300 ml of heparinized blood plasma were recirculated in vitro over a period of 4 hours with a plasma flow of 100 ml / min through a dialyzer with an effective exchange surface of 1 m2.
  • the C5a fragments in the plasma were determined using the RIA method (Upjohn test).
  • the relative complement activation for the respective time of measurement was calculated by forming the ratio of the concentration at the time of sampling with the initial value in percent. The measured value after 4 hours of recirculation was used for the evaluation.
  • Flat membranes are used heparinized blood plasma incubated for 3 hours and then the C5a fragments determined.
  • Thrombogenicity was assessed using TAT (thrombin-anti-thrombin) and PC (platelet count).
  • the increase in the beta-2 microglobulin level in long-term dialysis patients is observed after using membranes made from regenerated cellulose and is attributed to the fact that these membranes are less permeable in the molecular range from 1000 to 20,000 and the microglobulins are therefore not removed to a sufficient extent during dialysis become.
  • the beta-2-microglobulin is not adsorbed to any appreciable extent on the usual membranes made from regenerated cellulose.
  • the cellulose derivatives according to the invention can contribute to this in an unexpected manner.
  • the average degree of polymerization DP was determined in a Cuen solution according to DIN 54270.
  • the degree of etherification was determined on the basis of the analysis results which are known and typical of the substituents, for example nitrogen according to Kjeldahl, sulfur according to Schöniger and alkyl or aryl residues with the aid of NMR spectroscopy.
  • the object of the invention was therefore to provide reusable dialysis membranes made from very low-substituted cellulose derivatives, the biocompatibility properties of which are not impaired by the very low degree of substitution, which moreover have a thrombogenicity and heparin adsorption comparable to Cuprophan R and which also have higher substance concentrations can be produced much more economically using the known solvents.
  • the polysaccharide ether has a formula reproduced structure, in which Cell is the skeleton of the unmodified cellulose molecule or of the chitin molecule in each case without hydroxyl groups, s is 3 for the unmodified cellulose molecule and 2 for the chitin molecule and x corresponds to the degree of etherification, which is in the range from 0.001 to 0.079 and where R is a Alkyl, alkenyl, alkynyl, cycloalkyl and / or cycloalkenyl, cycloalkynyl, aryl, arylalkyl, arylalkenyl and / or arylalkynyl radical having 3 to 25 carbon atoms and / or the rest of a heterocyclic compound 3 to 25 carbon atoms, which can be substituted with the proviso that the substituent represents a non-ionic group OR ', SR
  • Preferred embodiments are characterized in the subclaims.
  • the properties of the membrane material such as, for example, the solubility in aqueous systems and the viscosity of such a solution, can be influenced via group R.
  • R corresponds to a benzyl, methylbenzyl, methoxybenzyl, chlorobenzyl, hexyl, dodecyl or octadecyl group.
  • R corresponds to a hydroxypropyl, hydroxybutyl, hydroxydodecyl, 2-hydroxypropylbutyl ether, 2-hydroxypropyldodecyl ether, 2-hydroxypropylcyclohexyl ether, 2-hydroxypropylbenzyl ether or 2-hydropropylphenyl ether group.
  • the dialysis membrane is preferably produced from an aqueous spinning solution which contains polysaccharide ether.
  • the aqueous spinning solution is preferably a Cuoxam solution.
  • the membrane can also be made from a water-borne N-oxide-tert.-amine spinning solution which contains polysaccharide ether.
  • the water-containing N-oxide-tert.-amine spinning solution is preferably an N-methylmorpholine-N-oxide solution.
  • the membrane can be produced from a lithium chloride-containing amidic organic solvent which contains the polysaccharide ether.
  • the lithium chloride-containing solvent is lithium chloride / dimethylacetamide or lithium chloride / N-methylpyrrolidone.
  • the spinning solution preferably contains 2 to 25% by weight of polysaccharide, but particularly preferably 5-15% by weight of polysaccharide.
  • the spinning solution preferably has a viscosity of 10 to 300 Pa.s.
  • the polysaccharide ether has a degree of polymerization (DP) of 200 to 5000.
  • the average degree of substitution (x) of the polysaccharide modified by substitution is said to be within the framework of the present invention, the average number of substituents per 1 anhydroglucose unit can be understood.
  • the desired average degree of substitution can be set by the molar ratio of polysaccharide to etherification reagent or by mixing differently substituted polysaccharides or substituted with unsubstituted polysaccharides.
  • Linters cellulose (DP: 1350 in cuen) were alkalized with 55.2 g (1.38 mol) of sodium hydroxide, dissolved in 250 ml of water, at 16 ° C. for one hour .
  • 250 ml of i-propanol and 58.19 g (0.46 mol) of benzyl chloride the mixture was stirred at 80 ° C. for six hours.
  • a cuoxam solution with a 9% by weight polysaccharide content was produced from this benzyl cellulose and processed into flat membranes in the laboratory. C5a activation is reduced by 95% compared to unmodified cellulose membrane. The thrombogenicity is comparable to that of the Cuprophan R.
  • the membranes do not absorb heparin according to the test specification of the German Kabi Vitrum GmbH, Diagnostika.
  • the benzyl cellulose from Example 1 was mixed with different amounts of unmodified Linters cellulose, dissolved in Cuoxam (9% by weight polysaccharide content) and processed in the laboratory to form flat membranes.
  • the mixing ratio and the C5a reduction achieved in comparison to unmodified cellulose membrane are summarized in Table 1.
  • Table 1 example Mixing ratio x C5a reduction% Benzyl cellulose parts Linters cellulose parts 2nd 20th 80 0.015 86 3rd 15 85 0.011 80 4th 10th 90 0.007 77 5 5 95 0.004 55
  • the membranes of Examples 2 to 5 had a thrombogenicity comparable to that of Cuprophan.
  • a Cuoxam spinning solution was prepared by a known procedure, which contained 9% by weight of benzyl cellulose, 8.3% by weight of NH 3 and 3.91% by weight of Cu. This was done by means of a hollow thread spinneret, the annular gap of which had an exit area of 0.47 mm2 and the inner filling feed of a diameter of 0.85 mm had spun into a hollow thread by the spinning solution together with isopropyl myristate as a void-forming inner filling emerged vertically downwards from the spinneret and, after an air gap of 4 cm, immersed in an aqueous precipitation bath at 40 ° C., which contained 110 g / l H2SO4. The amount of the spinning solution was 4.5 ml / min and the amount of the inner filling was 2.1 ml / min.
  • the hollow fiber solidified in the precipitation bath was passed through conventional baths with dilute sulfuric acid and water for regeneration and neutralization, passed through an aqueous glycerol bath at the end of the route and then dried on a drum dryer at 75 ° C. to a residual water content of 10.2%.
  • the glycerin content of the dry thread was 4.4%.
  • the breaking strength of this hollow thread was 119 cN with an elongation at break of 26.2%.
  • a Cuoxam spinning solution which contained 7.2% by weight of Linters cellulose, 1.8% by weight of the above-synthesized benzyl cellulose, 8.3% by weight of NH3 and 3.91% by weight of Cu.
  • the hollow thread solidified in the precipitation bath was used for regeneration and neutralization by conventional baths dilute sulfuric acid and water, passed at the end of the route through an aqueous glycerol bath and then dried on a drum dryer at 75 ° C to a residual water content of 10.5%.
  • the glycerin content of the dry thread was 4.5%.
  • the breaking strength of this hollow thread was 118 cN with an elongation at break of 28.2%.
  • the hollow thread was processed into test specimens, on which the following data were determined: UFR: 5.64 ⁇ 10 ⁇ 2 ml / h ⁇ m2 ⁇ Pa (7.5 ml / h ⁇ m2 ⁇ mm Hg) DL-Vit.B12: 6.8 cm / min ⁇ 10 ⁇ 3 DL creatinine: 56.5 cm / min ⁇ 10 ⁇ 3
  • a Cuoxam spinning solution of the same composition as in Example 7 was spun into hollow fibers in an aqueous precipitation bath at 40 ° C, which contained 110 g / l H2SO4.
  • the hollow thread solidified in the acidic precipitation bath passed through all conventional baths and the drum dryer as in Example 7.
  • DL-Vit.B12 6.5 cm / min ⁇ 10 ⁇ 3 DL creatinine: 52 cm / min ⁇ 10 ⁇ 3 Sieving coefficient for albumin: 0 Sieving coefficient for cytochrome-C .: 0.11
  • the mechanical data remained almost unchanged, namely breaking strength 124 cN and elongation at break 27.8%.
  • the wall thickness was 7.9 ⁇ m and the inside diameter was 198 ⁇ m.
  • C5a activation is reduced by 88%.
  • the thrombogenicity is comparable to that of the Cuprophan R.
  • a Cuoxam spinning solution with a content of 4.9% by weight of Linters cellulose, 1.3% by weight of benzyl cellulose from Example 6, 8.5% by weight of NH3 and 2.6% by weight of Cu was prepared. This was spun into a hollow thread by means of a hollow thread nozzle with an outlet slot of 0.08 mm2 area and an inner filling bore of 0.25 mm diameter, so that the spinneret 18 cm below the surface of the precipitation bath with the outlet openings pointing upwards was appropriate. Dry nitrogen served as the inner filling. The amount of the spinning solution was 7.0 ml / min and the amount of nitrogen was 2.0 ml / min at a pressure of 22 mbar.
  • the hollow thread emerging from the submerged spinneret was passed vertically upwards through the precipitation bath and deflected at a height of 30 cm above the bath level for further treatment in the machine direction.
  • the hollow fiber contained a residual amount of 16% water and a glycerol content of 52%.
  • the wall thickness was 18.2 ⁇ m and the inner diameter was 204 ⁇ m with a breaking force of 62 cN and an elongation at break of 52%.
  • a Cuoxam spinning solution of the same composition as in Example 7 was spun into a hollow thread with a spinneret immersed and an internal nitrogen filling using the same spinning arrangement as in Example 9.
  • the spinneret had an exit area of 0.06 mm2, the bore of the inner fill feed was 0.25 mm in diameter.
  • the plasticizer bath contained an aqueous solution of 9 g / l glycerol.
  • the dry hollow fiber had a wall thickness of 8.1 microns and an inner diameter of 202 microns, the glycerol content was 4.8%.
  • the hollow fiber membrane showed the following performance: UFR: 4.59 ⁇ 10 ⁇ 2 ml / h ⁇ m2 ⁇ Pa (6.1 ml / h ⁇ m2 ⁇ mm Hg) DL-Vit. B12: 7.1 cm / min ⁇ 10 ⁇ 3 DL creatinine: 56 cm / min ⁇ 10 ⁇ 3 Sieving coefficient for albumin: 0 Sieving coefficient for cytochrome-C: 0.14
  • C5a activation is reduced by 89%.
  • the thrombogenicity is comparable to that of Cuprophan R.
  • a Cuoxam spinning solution of the composition as in Example 7 was placed on a Cuprophan flat caster with a casting width of 60 cm and a casting slot width of 0.25 mm in an aqueous precipitation bath containing 90 g / NaOH, 6 g / l NH3 and 0.8 g / l contained Cu, poured in such a way that the spinning solution emerging from the flat caster fell through an air gap of 18 mm in width, then immersed in the coagulation bath to a depth of 80 cm and, after deflection at this point, passed a further 250 cm of the coagulation bath by means of a driven roller .
  • the result was a flat membrane with a width of 32 cm and a wall thickness of 14 ⁇ m with a residual moisture of 8.5% and a glycerol content of 32%.
  • the thrombogenicity was comparable to that of Cuprophan R.
  • the membrane did not absorb heparin.
  • a Cuoxam solution with 9% by weight benzyl cellulose content was prepared by a known procedure.
  • the viscosity ( ⁇ ) determined with an Ubbelohde viscometer according to equation 1 was 36 Pa.s.
  • ⁇ rel Lead time of the solution Lead time of the solvent
  • cellulose ethers listed in Table 2 were synthesized analogously to Examples 12 and 13, dissolved in Cuoxam and their viscosity determined. (Examples 14 to 17). As a comparison, Table 2 shows Linters cellulose (Example 18) and cellulose (Example 19). Table 2 example R x DP (in Cuen) Ether concentration (wt%) Viscosity Pa.s 14 Benzyl 0.05 850 9 24th 15 Benzyl 0.075 820 9 46 16 Dodecyl 0.008 900 12th 20th 17th Dodecyl 0.013 860 10th 25th 18 (Linter's cellulose) - - 1350 9 100 19 (pulp) - - 600 9 45
  • a Cuoxam spinning solution with a content of 5.89% by weight of Linters cellulose, 0.31% by weight of benzyl cellulose from Example 6, 8.5% by weight of NH3 and 2.6% by weight of Cu was prepared. This was spun into a hollow thread by means of a hollow thread nozzle with an exit slot of 0.08 mm2 area and an inner filling bore of 0.25 mm diameter, so that the spinneret was placed 18 cm below the surface of the precipitation bath with the outlet openings pointing upwards. Dry nitrogen served as the inner filling. The amount of the spinning solution was 7.0 ml / min and the amount of nitrogen was 2.0 ml / min at a pressure of 22 mbar.
  • the hollow thread emerging from the submerged spinneret was passed vertically upwards through the precipitation bath and deflected at a height of 30 cm above the bath level for further treatment in the machine direction.
  • the hollow fiber contained a residual amount of 16% water and a glycerol content of 52%.
  • the wall thickness was 18.2 ⁇ m and the inner diameter was 204 ⁇ m with a breaking force of 62 cN and an elongation at break of 52%.
  • a Cuoxam solution with 9% by weight polysaccharide content was produced from this product according to the usual procedure and processed in the laboratory to form flat membranes. Compared to unmodified cellulose membrane, the C 5a activation is reduced by 75%. Thrombogenicity and heparin absorption are comparable to those of standard Cuprophan R.
  • Example 21 Analogously to Example 21, the cellulose derivatives listed in Table 3 were synthesized by reacting Linter's cellulose with butylglycidyl ether, benzylglycidyl ether, dodecylglycidyl ether, cyclohexylglycidyl ether, dodecane epoxide or 1,2-epoxy-3-phenoxypropane and processed and investigated from Cuoxam solutions to give flat membranes. Compared to unmodified cellulose membranes, the modified membranes show a reduced C 5a activation. Thrombogenicity and heparin absorption are comparable to those of standard Cuprophan R.

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Claims (15)

  1. Membrane de dialyse pour l'hémodialyse sous forme de feuilles planes, de feuilles en gaine ou de fibres creuses en éther de polysaccharide, caractérisée en ce que l'éther de polysaccharide a une structure représentée par la formule
    Figure imgb0010
     dans laquelle Cell représente le squelette de la molécule de cellulose ou de chitine non modifiées à l'exclusion des fonctions hydroxyle, s vaut 3 pour la molécule de cellulose non modifiée et 2 pour la molécule de chitine non modifiée et x correspond au taux d'éthérification qui est compris entre 0,001 et 0,079, et dans laquelle R représente un groupe alkyle, alcényle, alcynyle, cycloalkyle, cycloalcényle, cycloalcynyle, aryle, arylalkyle, arylalcényle et/ou arylalcynyle tous comportant de 3 à 25 atomes de carbone et/ou le résidu d'un composé hétérocyclique comportant de 3 à 25 atomes de carbone qui peut être substitué avec la condition que le substituant soit un groupe non ionique -OR', -SR', halogéno et/ou -R', où -R' représente un résidu H, méthyle, éthyle ou R, et la chaîne carbonée pouvant être interrompue par la présence d'atomes d'oxygène ou de soufre.
  2. Membrane pour dialyse conforme à la revendication 1 caractérisée en ce que R représente un groupe benzyle, méthylbenzyle, méthoxybenzyle, chlorobenzyle, hexyle, dodécyle ou octadécyle.
  3. Membrane pour dialyse conforme à la revendication 1 caractérisée en ce que R représente un groupe hydroxypropyle, hydroxybutyle, hydroxydodécyle, 2-hydroxypropylbutyléther, 2-hydroxypropyldodécyléther, 2-hydroxypropylcyclohexyléther, 2-hydroxypropylbenzyléther ou 2-hydroxypropylphényléther.
  4. Membrane pour dialyse conforme à une ou plusieurs des revendications 1 à 3 caractérisée en ce que x = 0,001 à 0,019.
  5. Membrane pour dialyse conforme à une ou plusieurs des revendications 1 à 3 caractérisée en ce que x = 0,071 à 0,079.
  6. Membrane pour dialyse conforme à une ou plusieurs des revendications 1 à 5 caractérisée en ce que la membrane est préparée à partir d'une solution à filer aqueuse contenant de l'éther de polysaccharide.
  7. Membrane de dialyse conforme à la revendication 6 caractérisée en ce que la solution à filer aqueuse est une solution dans le cuoxam (liqueur contenant de l'hydroxyde de cupritétrammine).
  8. Membrane pour dialyse conforme à la revendication 6 caractérisée en ce que la membrane est préparée à partir d'une solution à filer qui est une solution d'éther de polysaccharide dans une amine tertiaire N-oxydée contenant de l'eau.
  9. Membrane pour dialyse conforme à la revendication 8 caractérisée en ce que la solution à filer dans un composé N-oxydé contenant de l'eau est une solution dans la N-méthylmorpholine N-oxydée.
  10. Membrane pour dialyse conforme à la revendication 6 caractérisée en ce que la membrane est préparée à partir d'une solution d'éther de polysaccharide dans un solvant organique de type amide contenant du chlorure de lithium.
  11. Membrane pour dialyse conforme à la revendication 10 caractérisée en ce que le solvant contenant du chlorure de lithium est un mélange chlorure de lithium/diméthylacétamide ou chlorure de lithium/N-méthylpyrrolidone.
  12. Membrane pour dialyse conforme à la revendication 5 ou 6 caractérisée en ce que la solution à filer contient de 2 à 25 % en poids d'éther de polysaccharide.
  13. Membrane pour dialyse conforme à la revendication 12 caractérisée en ce que la solution à filer contient de 5 à 15 % en poids d'éther de polysaccharide.
  14. Membrane pour dialyse conforme à une ou plusieurs des revendications 6 à 13 caractérisée en ce que la solution à filer a une viscosité comprise entre 10 et 300 Pa.s.
  15. Membrane pour dialyse conforme à une ou plusieurs des revendications 1 à 14, caractérisée en ce que l'éther de polysaccharide a une degré de polymérisation (DP) compris entre 200 et 5000.
EP93108473A 1992-06-05 1993-05-26 Membrane pour dialyse à base d'éthers de polysaccharides Expired - Lifetime EP0572910B1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
DE19924218568 DE4218568A1 (de) 1992-06-05 1992-06-05 Dialysemembran aus Polysaccharidether II
DE4218568 1992-06-05
DE4315351 1993-05-08
DE4315351 1993-05-08

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EP0572910B1 true EP0572910B1 (fr) 1996-06-26

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EP (1) EP0572910B1 (fr)
JP (1) JP3329885B2 (fr)
DE (1) DE59303060D1 (fr)
ES (1) ES2089636T3 (fr)

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US6174443B1 (en) 1997-04-14 2001-01-16 The Research Foundation Of State University Of New York Purification of wheat germ agglutinin using macroporous or microporous filtration membrane
US5993661A (en) * 1997-04-14 1999-11-30 The Research Foundation Of State University Of New York Macroporous or microporous filtration membrane, method of preparation and use
US7094372B1 (en) * 2003-06-12 2006-08-22 Chung Yuan Christian University Chitosan membrane containing nano-inorganic particles and the method for forming the same
US20080296808A1 (en) * 2004-06-29 2008-12-04 Yong Lak Joo Apparatus and Method for Producing Electrospun Fibers

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US4308377A (en) * 1978-12-29 1981-12-29 Kureha Kagaku Kogyo Kabushiki Kaisha Shaped material comprising denatured chitin and process for preparing same
US4424346A (en) * 1981-06-04 1984-01-03 Canadian Patents And Development Ltd. Derivatives of chitins, chitosans and other polysaccharides
US5059654A (en) * 1983-02-14 1991-10-22 Cuno Inc. Affinity matrices of modified polysaccharide supports
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DE3524596A1 (de) * 1985-07-10 1987-01-15 Akzo Gmbh Dialysemembran aus modifizierter cellulose mit verbesserter biokompatibilitaet
EP0319938B1 (fr) * 1987-12-11 1996-05-08 Akzo Nobel N.V. Cellulose modifiée pour des membranes de dialyse biocompatibles
EP0339200A1 (fr) * 1988-02-25 1989-11-02 Akzo Nobel N.V. Cellulose modifiée, son utilisation comme membranes biocompatibles II pour la dialyse, et procédé pour sa préparation
DE3814326A1 (de) * 1988-04-28 1989-11-09 Akzo Gmbh Verfahren zur modifizierung von cellulosischen dialysemembranen zur verbesserung der biocompatibilitaet und vorrichtung zur durchfuehrung des verfahrens
DE3826468A1 (de) * 1988-08-04 1990-02-15 Akzo Gmbh Dialysemembran fuer die haemodialyse aus regenerierter, modifizierter cellulose
DE3842822A1 (de) * 1988-12-20 1990-07-05 Akzo Gmbh Biocompatible dialysemembran aus einem gemischten polysaccharidester
DE4017745A1 (de) * 1990-06-01 1991-12-05 Akzo Gmbh Dialysemembran aus polysaccharidether
DE59208184D1 (de) * 1992-01-07 1997-04-17 Akzo Nobel Nv Verfahren zum Beschichten cellulosischer Membranen

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EP0572910A1 (fr) 1993-12-08
ES2089636T3 (es) 1996-10-01
JPH06142473A (ja) 1994-05-24
US5427684A (en) 1995-06-27
JP3329885B2 (ja) 2002-09-30

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